The aim of the study was to determine the efficacy of recombinant human interferon lambda against human adenovirus serotype 5 in a culture of human conjunctival cells Chang conjunctiva clone 1-5c-4 (in vitro) and in primary culture of human corneal epithelial cells (ex vivo). Materials and methods. The study design consisted of three experimental schemes, reflecting a prophylactic and two options for a therapeutic and prophylactic treatment regimen (with the constant presence of the virus in the culture medium and with its removal after adsorption). The antiviral activity of interferon lambda was determined by the number of viable cells after exposure to the virus (MTT test). Results and discussion. It has been established that interferon lambda has antiviral activity against human adenovirus in vitro and ex vivo under a prophylactic and therapeutic-prophylactic scheme of administration at an infection dose of 1 and 10 TCID 50 , but not at an infection dose of 100 TCID 50 . The antiviral effect of the use of interferon lambda in a therapeutic and prophylactic regimen at an infection dose of 1 TCID 50 was comparable to that of interferon alpha. At the same time, interferons lambda and alpha did not have a toxic effect on the cell culture even at a concentration of 84 μg/ml and 58 μg/ml, respectively. The antiviral activity and the absence of cytotoxic action create the basis for further study of the antiviral action of interferon lambda in order to develop a drug based on it for the treatment of viral diseases of an eye surface.

Несмотря на значительные достижения в создании лекарственных средств, на сегодняшний день не существует эффективных универсальных препаратов для лечения вирусных инфекций. Это стало очевидным в ходе пандемии, вызванной COVID-19. Одним из потенциально возможных противовирусных средств являются интерфероны, которые уже зарекомендовали себя как эффективные препараты для лечения заболеваний, вызванных вирусами. В данной работе рассматривается возможность использования рекомбинантного человеческого интерферона лямбда-1 и его пегилированной формы для лечения инфекции, вызванной SARS-CoV-2. В ходе экспериментов на культуре клеток Vero E6 было выявлено, что фармацевтическая субстанция на основе рекомбинантного человеческого интерферона лямбда-1, иммобилизованного на ПЭГ 1500 методом электронно-лучевого пегилирования, обладает выраженной противовирусной активностью и высоким терапевтическим индексом в отношении SARS-CoV-2, а также обладает низкой цитотоксичностью в отношении культуры клеток Vero E6. Полученные данные позволяют считать, что на основе данной субстанции возможно создание лекарственного препарата для лечения вирусной инфекции, вызываемой SARS-CoV-2.

Интерферон лямбда относится к относительно недавно открытому III типу интерферонов и вызывает большой интерес, поскольку обладает рядом уникальных свойств, обусловленных его филогенетическим происхождением. Данный обзор посвящен биологической активности эндогенного интерферона лямбда, в частности рассматриваются механизмы его индукции и экспрессии различными тканями и клетками организма человека — от взаимодействия со специфичными рецепторами до начала транскрипции посредством активации сигнальных путей. Поскольку известно, что интерфероны обладают противовирусной активностью, то отдельное внимание уделено тканеспецифическим эффектам в желудочно-кишечном, респираторном и урогенитальном трактах. Освещено иммуномодулирующее действие интерферона лямбда и его роль при аутоиммунных заболеваниях, а также противоопухолевые эффекты интерферона лямбда. Проводится сравнение функций интерферона лямбда с относительно хорошо изученными интерферонами первого типа. Показана противовирусная активность интерферона лямбда на структурах гематоэнцефалического и плацентарного барьеров.

The development of effective antiviral drugs for use in ophthalmic practice is an urgent task of modern medicine. Type III interferons have similar functions with wellknown type I interferons, that is they have antiviral, antitumor and immunomodulating activities. However, their receptors are expressed primarily on epithelial barrier cells, such as mucous membranes. In this regard, type III interferons have less systemic side effects when used for therapeutic purposes. However, interferons are protein molecules, which mean that they are practically not absorbed from gastrointestinal tract, therefore, they need parenteral administration, which reduces patient compliance. It was shown that electron-beam pegylation increases the solubility of the original substances, reduces immunogenic properties, and also increases the oral bioavailability of proteins up to 20%. However, a change of the molecule structure can significantly change both pharmacokinetic and pharmacodynamic properties. In this work the allergenic properties of interferon1, pegylated by electron beam method, were investigated in the systemic anaphylaxis reaction in guinea pigs, and in the active cutaneous anaphylaxis reaction and the conjunctival test in mice. Thus, it was found that pegylated IFN-λ1, obtained by the electron beam method, generally does not have allergenic properties when used in a therapeutic dose or in ten-fold higher dose, in the conditions of the experiments. This creates the prerequisites for the development of a drug based on pegylated IFN-λ1 for the treatment of viral infections of the ocular surface, and it requires further experiments to establish its effectiveness.

Drugs based on interferon α-2b are highly effective in parenteral administration. When administered per os, their effectiveness is significantly less. Electron-beam immobilization of interferons α-2b allows to improve pharmacokinetic characteristics when taking per os. In the chamber of Ussing a high rate of absorption of immobilized interferon α-2b (imINFα-2b) in the bowels up 5.46 ng/cm 2 was estimated. In vivo experiments established that imINFα-2b is actively absorbed from the lumen of the jejunum exclusively into the blood system. It was determined that imINFα-2b concentration in v. mesenterica after 1h incubation 1.5-fold higher that native form of INFα-2b. Unlike native INFα-2b, the imINFα-2b has better pharmacokinetic characteristics, so imINFα-2b almost unchanged concentration passes through the liver, and passing through the kidneys, its concentration increases to a value of 7.18±0.66 ng/L. on the basis of the pharmacokinetic parameters of imINFα-2b, such as the average retention time in the rat (MRT) - 9.98 hours; half-life (T 1/2 ) - 6.28 hours; maximum concentration (Cmax) -15.61 ng/mL; time to reach (Tmax) is 4 hours; average time of suction - 3.58 hours and clearance of 23.90 mL/HR, it can be argued that imINFα-2b is the real prototype of the oral medicines.

Purpose: To estimate the stabilizing effect of orthokeratology lenses (ortho-K, OK-lenses) on myopia progression by evaluating axial eye growth dynamics and clinical refraction. Material and methods. Ortho-K group consisted of 68 children (135 eyes) aged 7–17 years (mean age 12.2) with progressive myopia (initially -0.75–6.75 D). Observation period varied from 7 to 30 months (mean period 11.68±4.39). All patients used OK-lenses for overnight wear. The control group consisted of 90 patients (180 eyes) with myopia who were prescribed single vision spectacles for vision correction. Comparative analysis was performed for clinical refraction parameters as well as for axial length (AL). The data was obtained with the use of IOL-Master optical biometer (“Carl Zeiss”). Results. The parameters were stable in patients of ortho-K group: axial length, subjective and objective clinical refraction, the required power of corrective lenses. However, the parameters changed significantly in the control group during the observation period: uncorrected visual acuity (UCVA) decreased, the required power of corrective lenses increased, the indices of objective clinical refraction strengthened, annual gradient of progression (AGP) amounted to 0.26±0.19 and 0.16±0,39 mm in patients with low and moderate myopia, respectively. Conclusion. The use of OK-lenses ensures a significant deceleration of myopia progression in children. The results obtained suggest a wider use of ortho-K among pediatric ophthalmologists in their clinical practice as it is an effective preventive and therapeutic method for patients with progressive myopia.